7. Women who
are breastfeeding can still be
immunized (passive-active
immunization, live or killed
vaccines). (II-1)

8. Pregnant
women should be offered the
influenza vaccine when pregnant
during the influenza season. (II-1)

INTRODUCTION

Immunization programs are among the
most cost-beneficial health
interventions. As women who are
considering pregnancy or who are
already pregnant present for health
care consistently, obstetrical care
providers are well placed to review
their immunization status and
recommend vaccination strategies.
This can significantly reduce the
occurrence of preventable diseases,
benefiting not only the patient and
her infant but also the rest of the
population. As pregnancy is
considered to be an immunologically
competent status, a full and
unaltered response to immunization
is expected.1,2

The obstetrical care provider
counsel the pregnant woman with
respect to the risks and benefits of
vaccines, as well as potential
exposure to the diseases the
vaccines are expected prevent.
Appropriate information and
counseling must also be provided in
cases of inadvertent vaccination in
pregnancy. This document reviews
active and passive immunization,
indications for and
contraindications to such
interventions in pregnancy, and
suggested precautions. Finally,
specific vaccines are discussed and
recommendations made their use in
pregnancy (Table 2).

General
Comments

Prenatal care providers should
obtain a thorough immunization
history. In many cases, women
present for prenatal care having not
had their immunization status
reviewed since they completed the
school-age vaccination schedule.
Ideally, women should have their
vaccination status optimized
pre-pregnancy, so there would be no
concern about coverage in pregnancy.
However, if this is not possible,
planning for vaccination in
pregnancy with killed or recombinant
vaccines or planning for vaccination
post partum with live-attenuated
vaccines is appropriate. Prenatal
care providers should also be aware
of the risks, if any, of inadvertent
vaccination during pregnancy.

The overall
objective of immunization in
pregnancy is to induce a state of
immunity such that the woman and the
fetus are protected following
exposure to the offending organism.
In addition, this offers an
opportunity for protection of the
neonate for the first 6 to 12 months
of life. Vaccines may be prepared
from various sources, including the inactivated
agent, live attenuated agent, and
modified and single antigen
recombinant forms of the offending
organism.

Immunizations can be either active
or passive, depending on the
characteristics of the agent used.
Passive immunization is a process
whereby the agent used has been
obtained from serum from either a
person or an animal already
adequately immunized. From this
process, antibodies can be obtained
either as whole serum or as
concentrated IgG and may be
administered to the host to confer
immediate protection.

Active
immunization relies on the
administration of antigens and
results in a prompt but transient
IgM response in the host. This is
followed by a rise in IgG antibody
production

that will be
more or less sustained, explaining
why for some vaccines, booster doses
may be required for long-term immune
memory. Of note, oral vaccines will
stimulate IgA initially as opposed
to IgM (parenteral).

Given the theoretical fetal risks
associated with maternal
immunization, an evaluation of
potential risks of exposure to the
infectious agent, as well as
benefits of vaccination

REVIEW OF
SPECIFIC VACCINE CATEGORIES

Live and
Live-Attenuated Vaccines

In general, live and/or
live-attenuated virus vaccines are
contraindicated during pregnancy, as
there is a primarily theoretical
risk to the fetus. However, it is
important to mention that, to date,
there is no evidence to demonstrate
a teratogenic risk from any
currently available vaccines (e.g.,
mumps, measles, rubella varicella).3,4

Rubella
vaccine

The rubella virus is moderately
infectious and clinically manifests
as fever, malaise, lymphadenopathy,
and upper respiratory symptoms
followed by the appearance of a
typical rash. Complications are more
common in the adult and include
arthralgia, arthritis, encephalitis,
neuritis, and thrombocytopenic
purpura. CRS is particularly severe
and more common if it occurs early
in pregnancy, with up to 85% of
infants affected if infected in the
first trimester. CRS may result in
deafness, cataracts, cardiac
defects, microcephaly, mental
retardation, hepatosplenomegaly,
bone damage, and thrombocytopenia.
Furthermore, the effects may be
delayed by several years, and
children may present with diabetes
or a progressive encephalopathy. The
best way to eradicate CRS is to
immunize all susceptible women and
women without adequate proof of
immunization.

The obstetrical care provider is in
a good position to identify
susceptible women and to provide
immunization post partum. The
rubella vaccine alone and in
combination (MMRII) is a live
vaccine and therefore
contraindicated during pregnancy. It
is therefore suggested that women
should delay pregnancy by one month
following such immunization.

Inadvertent vaccination in pregnancy
was reportable to the Centers for
Disease Control and Prevention
between 1971 and 1989. Analysis of
the accumulated data revealed that
subclinical infection was detected
in 1% to 2% of fetuses but that
there was no evidence of CRS in any
of the 321 women inadvertently
vaccinated who elected to continue
their pregnancies.5 Therefore, in
such situations, women should be
reassured that ending the pregnancy
is not necessary on the basis of
fetal risks following maternal
immunization. However, given the
small theoretical fetal risk,
immunization with the rubella
vaccine is best delayed until after
delivery. Neither breastfeeding nor
anti-Rho(D) administration is a
contraindication to immunization.

Varicella
vaccine

Although varicella is relatively
uncommon in the pregnant population
(0.7 per 1000), it can result in
very significant maternal and fetal
morbidity and mortality. Despite
improvements in clinical care,
varicella may be complicated by
pneumonia in up to 28% of pregnant
women, and this remains associated
with a risk of mortality. In a
recent report of 198 cases of
varicella in pregnancy, 16 deaths
were reported, all in the group
complicated by pneumonia.6
Furthermore, varicella in early
pregnancy is associated with a 1%
risk of congenital infection, which
carries serious sequelae such as
cerebral cortical atrophy, mental
retardation, and dermatomal specific
limb abnormalities.7 Maternal
varicella occurring five days before
to two days after delivery is
associated with severe neonatal
varicella in 17% to 30% of infants
and a case fatality rate as high as
31%.8 These facts highlight the
importance of adequate immunization
in women of childbearing age and the
influence obstetrical care
practitioners can exert on the
prevention of varicella in mother
and fetus.

Immunity to varicella should be
reviewed in the context of maternal
health care, and vaccination should
be recommended as soon as
appropriate. Since the varicella
vaccine is an attenuated virus
vaccine (two preparations are
available in Canada and both are
live), it should not be given in
pregnancy. A program of
administration to susceptible post
partum women should be developed. A
second dose is recommended and should be
administered approximately four
weeks after the first.9
Breastfeeding is not a
contraindication to vaccination, nor
is household contact with a newborn.
A study of 362 women inadvertently
exposed to varicella vaccine in
pregnancy between 1995 and 2000
identified no cases of congenital
varicella.10 It therefore does not
constitute a reason to
recommend pregnancy termination.
Instances of inadvertent varicella
immunization during pregnancy or of
pregnancy occurring within three
months after immunization should be
reported to the pharmaceutical
company.

Non-pregnant women who are
vaccinated should delay conception
by one month. Following exposure of
a pregnant woman to varicella, a
history of previous vaccination or
of chickenpox itself should be
sought, as it has been shown to
correlate with immune status. In the
absence of such a history, the
mother’s immunity should be
determined. Susceptible women should
then be offered varicella zoster
immune globulin within 96 hours of
exposure in an attempt to prevent
the disease or reduce the severity
of the infection in the mother. The
recommended dosage is 125 units/10
kg to a maximum of 625 units.
Although there may also be some
benefit to the fetus, this remains
to be investigated in a clinical
trial.

Benefits
versus risks

Given the possible risks, live and
live-attenuated vaccines should not
be given in pregnancy unless there
are special circumstances and the
benefits clearly outweigh the
theoretical risks. For example, if a
pregnant woman must travel to an
endemic area for yellow fever, the
vaccine may need to be administered,
even though it is a live attenuated
vaccine, when the risk of exposure
is high and the travel cannot be
postponed. A recent report of 304
pregnant women exposed to yellow
fever immunization in early
pregnancy demonstrated that such
exposure was not associated with an
increase in major fetal
malformation.11

Inactivated
Viral Vaccines, Bacterial Vaccines,
and Toxoids

These vaccines are considered safe
in pregnancy. The possible benefit
of immunizing pregnant women must
always be balanced against the
potential risks of the vaccine. As
there is no evidence to suggest a
risk to the fetus or to the
pregnancy from maternal immunization
with these agents, the benefit of
their use generally far outweighs
the theoretical risks.

Influenza
vaccine

Influenza is a highly contagious
acute respiratory infection. It is
manifested clinically as an abrupt
onset of malaise, headache, and
myalgia followed by a cough, fever,
and sore throat. There is literature
that suggests that pregnant women
are at increased risk of
complications from influenza.12,13
Pregnancy is associated with
significant cardiovascular and
respiratory demands, as evidenced by
increases in stroke volume, heart
rate, and oxygen consumption. This
is highlighted in a 1998 study,
which reported that the need for
hospitalization was four times
greater in pregnant than
non-pregnant women with influenza.14

The risks were in fact calculated to
be equivalent to those of
non-pregnant women with high-risk
conditions, for whom immunization
has traditionally been recommended.
Older data12,13 also suggest
increased maternal risk, as previous
reports of pandemics showed that
morbidity and mortality was greater
in pregnant women. Although the data
are limited and more research is
needed to clarify the maternal-fetal
risks of influenza, current
recommendations support immunization
of pregnant women with the
inactivated vaccine. There is debate
about the appropriateness of
immunization in the first trimester,
so it may be prudent to delay
immunization until the second
trimester unless there is an
immediate risk of transmission.
Influenza is not known to be teratogenic. No adverse effects on
perinatal outcome were observed in a
cohort of 252 women vaccinated at a
mean gestational age of 26.1
weeks.15 Current Canadian
recommendations advocate universal
immunization of pregnant women
against influenza.

Another reason for immunization in
pregnancy is the protection of the
newborn after birth, which can be
accomplished with passive immunity
(transfer of maternal antibodies).
Further, the most common way for
infants to acquire influenza is from
household contacts, so immunization
of the mother can prevent her from
acquiring influenza and potentially
passing it on to her child.

Other
Vaccines

Human
papilloma virus

In Canada, the quadrivalent HPV
vaccine was approved in July 2006
for the prevention of infection by
HPV strains that are responsible for
70% of cervical cancers and 90% of
genital warts. In February, 2007,
after serious consideration, the
National Advisory Committee on
Immunization issued recommendations
for the use of Gardasil for females
aged 9 to 26. Gardasil vaccine is
manufactured using recombinant
technology and uses a specific
subunit of the virus L1, which then
assembles into non-infectious
virus-like particles. It
specifically targets HPV 6, 11, 16,
and 18, which are known to be
associated with cervical, vulvar,
and vaginal cancers and genital
warts. Although the vaccine is not
recommended for use during
pregnancy, there is no evidence that
it is teratogenic16. If woman
becomes pregnant part way through
the vaccine series, it is
recommended that the rest of the
series be deferred until after
pregnancy. The vaccine can be
administered to women who are
breastfeeding.16

SIDE EFFECTS
AND CONTRAINDICATIONS

Vaccines may cause various side
effects, which should not all be
interpreted as contraindications.
Side effects can be divided in five
categories:

(1)immediate/early,

(2)local,

(3)systemic,

(4)allergic, and

(5)long-term

1.
Immediate/early effects include
fainting and vasovagal reactions.
These are differentiated from
anaphylactic shock (see below).
Patients who have received the
vaccine should be kept in the
waiting room for observation for 5
to 10 minutes.

2. Local
effects are mild and are the most
common. They include soreness,
erythema, and swelling.

3. Systemic
effects are less common and include
malaise and fever.

4. Mild
allergic reactions can also occur.
In general, these will be in
reaction to exposure to avian
proteins (eggs, such as in yellow
fever) or to traces of
neomycin/streptomycin (MMR).
Anaphylactic reactions are
exceedingly rare. They should be
recognized immediately and treated
following local protocols with
injection of sc epinephrine
(1:1000).

5. Long-term
complications such as Guillain-Barre
syndrome can occur but usually at
rates lower than that seen for
spontaneous disease. Unfortunately,
too often, vaccines are withheld on
the basis of what is thought to be a
contraindication.

The items on
this list DO NOT represent
contraindications to immunization

•Mild acute illness with or
without low-grade fever

•Autoimmune disorder, multiple
sclerosis

•Family history of
convulsions, epilepsy

•Recent exposure to an
infectious disease

•Current antimicrobial therapy
or convalescence from recent illness

•Household contact with
pregnant woman

•Breastfeeding

•Prior reaction to
immunization with mild/moderate
tenderness, redness, swelling, or
fever of less than 40°C

•Personal history of
allergies, excluding anaphylaxis, to
neomycin/streptomycin or egg protein

•Family history of adverse
reaction or allergies to vaccines

•Positive TB skin test

Household
contact vaccination and
breastfeeding

Although individuals immunized with
live virus vaccines can shed the
virus, they will not transmit it;
therefore, household contacts of
pregnant women can be safely
vaccinated without risks to the
mother and her fetus. Breastfeeding
is also considered safe following
immunization of the mother, and it
has not been shown to adversely
influence the maternal immune
response. Therefore, breastfeeding
does not represent a
contraindication to any
immunization: passive-active
immunization, live vaccines, or
killed vaccines.

Recommendations

The quality of evidence reported in
this document has been assessed
using the Evaluation of Evidence
criteria in the Report of the
Canadian Task Force on Preventive
Health Care17 (Table 1).

1. All women of
childbearing age should be evaluated
for the possibility of pregnancy
before immunization. (III-A)

2. Health care
providers should obtain an
immunization history from all women
accessing prenatal care. (III-A)

3. In general,
live and/or live-attenuated virus
vaccines are contraindicated during
pregnancy, as there is a, largely
theoretical, risk to the fetus.
(II-3)

4. Women who
have inadvertently received
immunization with live or
live-attenuated vaccines during
pregnancy should not be counseled to
terminate the pregnancy because of a
teratogenic risk. (II-2)

5. Non-pregnant
women immunized with a live or
live-attenuated vaccine should be
counseled to delay pregnancy for at
least four weeks. (III)

7. Women who
are breastfeeding can still be
immunized (passive-active
immunization, live or killed
vaccines). (II-1)

8. Pregnant
women should be offered the
influenza vaccine when pregnant
during the influenza season. (II-1)

CONCLUSION

The development of new vaccines and
the accumulating information about
vaccine safety ensure that
obstetrician-gynecologists can
provide immunizations and/or advice
about immunization for their
pregnant patients. This is most
important in disease prevention, and
obstetrician-gynecologists must play
an active role in vaccine
administration. Furthermore, it is
imperative that more research
efforts be focused in the area of
immunization in pregnancy.

Centers for
Disease Control and Prevention.
Measles, mumps and rubella
vaccine use and strategies for
elimination of measles, rubella,
and congenital rubella syndrome
and control of mumps:
recommendations for the advisory
committee on immunization
practices (ACIP). MMWR Recomm
Rep 1998;47(RR-8).